Efficacy of Zavegepant Nasal Spray for the Acute Treatment of Migraine Based on Triptan Treatment Experience: Pooled Results From 2 Randomized, Placebo-Controlled Clinical Trials

Efficacy of Zavegepant Nasal Spray for the Acute Treatment of Migraine Based on Triptan Treatment Experience: Pooled Results From 2 Randomized, Placebo-Controlled Clinical Trials

Background: Zavegepant, an intranasal gepant, is likely to be used in people who do not respond to or cannot take triptans. ^1,2

Purpose/Objectives: The objective of this study was to compare the efficacy of zavegepant nasal spray with placebo in the acute treatment of migraine based on historical and current triptan experience.

Method:

Post-hoc subgroup analysis based on the pooled results of 2 randomized, double-blind clinical trials comparing the efficacy of zavegepant nasal spray with placebo in the acute treatment of a single migraine attack of moderate to severe pain intensity. Subgroups reporting a history of an insufficient response to ≥1 triptan, current triptan users without a history of insufficient response, and triptan-naïve participants were analyzed. Co-primary efficacy endpoints were pain freedom and freedom from the most bothersome symptom (MBS) at 2 hours post-dose. Treatment groups were compared using nominal p-values. 

Results: In the pooled population (N=2061; zavegepant n=1014, placebo n=1047), 608 (29.5%) participants had a history of insufficient response to ≥1 triptan (zavegepant=307 [30.3%], placebo=301 [28.7%]), and 1453 (70.5%) had no history of insufficient response to triptans (current use=371 [18.0%], triptan-naïve=1082 [52.5%]). Zavegepant was effective on the coprimary endpoints in current triptan users (pain free: 21.0% vs 11.9%, p=0.0254, MBS free: 40.0% vs 29.5%, p=0.0440); participants who were triptan-naïve (pain free: 24.8% vs 17.4%, p=0.0029, MBS free: 40.4% vs 34.0%, p=0.0303); and those with insufficient response to ≥1 triptan (pain free: 21.8% vs 12.6%, p=0.0024; MBS free: 41.0% vs 29.9%, p=0.0035).

Conclusions: Zavegepant nasal spray was effective on both coprimary endpoints for the acute treatment of migraine in adults with and without a history of insufficient response to triptans and current triptan users.

References: 1. Zavzpret (zavegepant) prescribing information. Pfizer Labs; 2023.
2. Rissardo JP and Caprara ALF. Brain Sciences. 2022;12:1612

Disclosures: This study was sponsored by Biohaven, which was acquired by Pfizer in October 2022. Shivang Joshi has served a speaker for Abbvie, Amgen, Lilly, Teva, Impel, and Biohaven; has served as a consultant/advisor for Abbvie, Amgen, Lilly, Teva, Currax, Relivion, Nerivio, Axiome, Biohaven, and Lundbeck. Timothy Smith has served as a speaker for Amgen, Allergan/Abbvie, Biohaven, Novartis, and Lilly; has served as an advisor or consultant for Allergan/Abbvie, Biohaven, Amgen, Lilly, Alder/Lundbeck Impel Neuropharma, Neurolief, Nocira, Theranica, Teva, and Vorso/Nesos; and has received research support from Amgen, Alder/Lundbeck, Lilly, Teva, Allergan/Abbvie, Biohaven, Electrocore, Novartis, Novo Nordisk, Impel Neuropharma, Aeon, Charleston Labs, Nocira, Teva, Theranica, and Vorso/Nesos. Jelena M Pavlovic Has received research support from the NIH; serves as a consultant/advisory board member, or received honoraria from Allergan/AbbVie, Amgen, Biohaven, and Lundbeck/Alder. Kathleen Mullin serves as a consultant, advisory board member, or has received honoraria from Amgen, Teva, Theranica, Vorso, Biohaven, electroCore, and Eli Lilly. Robert Croop serves as a consultant to Pfizer; was employed by Biohaven at the time the clinical study was conducted; was employed by Pfizer at the time the analysis was conducted; and owns stock in Biohaven Ltd. Jennifer Madonia was an employee of Biohaven at the time the clinical study and analyses were conducted and owns stock/options in Biohaven Ltd. Linda Mosher was an employee of Biohaven at the time the clinical study was conducted; is currently an employee of Pfizer; and owns stock/options in Pfizer and Biohaven Ltd. Meghan Lovegren and Micaela Forshaw are employees of, and owns stock/options in, Biohaven. Richard B Lipton serves on editorial boards (no renumeration) for Neurology, Cephalalgia; serves as a Senior Advisor (no renumeration) to Headache; has received research support from the NIH, FDA, National Headache Foundation, and Marx Foundation; has received research grants from Allergan/AbbVie, Amgen, and Novartis; serves as a reviewer for the NIA and NINDS; serves as a consultant/advisory board member or receives honoraria from AEON, Allergan/AbbVie, Amgen, Biodelivery Sciences International Biohaven, CoolTech LLC, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, GlaxoSmithKline, Impel Neuropharma, Lundbeck Manistee, Merck, Novartis, Satsuma, Teva, and Vedanta; receives royalties from Wolff’s Headache (8th ed), Informa; and owns stock/options in Biohaven and Manistee.